Isothiazolinone compounds are a novel kind of potent and broad-spectrum antiseptics possessing the advantages of high potency, low toxicity, a long effective period and harmlessness to the environment over conventional antiseptics. Therefore, isothiazolinone compounds have broad applications in the fields of water treatment, cosmetics, construction materials, binding agents, paints, medical treatment, fabrics, photographs and detergents, and especially can be used as antifouling agents in marine antifouling coatings.
Till now, a number of methods for preparing N-substituted isothiazolinone derivatives have been reported, most of which comprise the step of reacting a N,N′-bis-substituted dithiodipropionamide or a N-substituted mercaptopropionamide with a halogenating agent in an organic solvent.
For example, Chinese Patent Applications CN1634889 and CN1629148 disclose, respectively, processes for preparing N-alkoxy propylisothiazolinones and N-alkoxyethoxyl propylisothiazolinones, which comprise reacting the corresponding N,N′-bis-substituted dithiodipropionamides with sulfuryl chloride in ethyl acetate.
Japanese Patent Application JP2003-335763 discloses a process for the preparation of 2-substituted-4-isothiazolin-3-ones, which comprises reacting N-substituted mercaptopropionamides or N,N′-bis-substituted dithiodipropionamides with a halogenating agent in ethyl acetate.
European Patent Application EP0498347 discloses a process for the preparation of 2-methyl-isothiazolin-3-ones, which comprises reacting N-methyl-3-mecaptopropionamides with chlorine in a solvent of aromatic or halogenated hydrocarbon, such as benzene, toluene, chlorobenzene, chloroform and the like.
European Patent Application EP1113012 discloses a process for the preparation of 2-alkyl-4-isothiazolin-3-ones, which comprises reacting N-alkyl mecaptopropionamides or N,N′-dialkyl dithiodipropionamides with a chlorinating agent in a solvent, in which hydrogen chloride is insoluble or has low solubility, such as halogenated aliphatic hydrocarbons, halogenated aromatic hydrocarbons or aliphatic hydrocarbons.
U.S. Pat. No. 5,453,507 discloses a process for the preparation of N,N′-dimethyl or N,N′-di-n-octyl-4-isothiazolin-3-ones, which comprises reacting N,N′-bis-substituted dithiodipropionamides with sulfuryl chloride in a halogenated organic solvent, such as CH2X2, CHX3, CX3CH3 and CHX2CHX2.
However, the use of organic solvents in the processes of the prior art causes a lot of problems. For example, firstly the use of the solvent will decrease the volumetric efficiency of the reactor thereby decreasing the productivity; secondly the post-treatment and recovery of the solvent will increase the operation cost; thirdly the solvent will bring impurities into the reaction system thereby complicating the separation and purification of the desired products; and lastly the organic solvent used, especially benzene and halogenated hydrocarbons, generally has an adverse effect on the environment.